Successful bone marrow transplantation in two sisters with activated phosphoinositide 3-kinase δ syndrome 2.

Abstract

Phosphoinositide 3-kinase (PI3K) signaling promotes diverse intracellular responses including proliferation, survival and differentiation. Class IA PI3K is a heterodimer, composed of p110 (catalytic) and p85 (regulatory) subunits. One of the p110 catalytic subunits, p110δ, is encoded by PIK3CD, and its expression is restricted to leukocytes. Activated phosphoinositide 3-kinase δ syndrome (APDS) 1 is a primary immunodeficiency disease (PID) caused by gain-of-function mutations of PIK3CD and is associated with various infections, autoimmunity, lymphoproliferative disease (LPD), and malignancy.1 Recently, APDS2 caused by heterozygous mutations within splice acceptor and donor sites of exon 11 of the PIK3R1 gene, affecting all of the three subunits, p85α, p55α and p50α, was reported. Patients with APDS2 also have increased PI3K/Akt/mTOR (mammalian target of rapamycin) signals and clinical features observed in APDS1.2, 3, 4, 5, 6, 7 Haematopoietic stem cell transplantation (HSCT) is one of available treatments to achieve long-term immune reconstitution and to prevent malignancy. Here, we report successful HSCT in two sisters with APDS2 suffering from EBV-associated lymphoproliferation.